Nerve growth factor- and neurotrophin-3-releasing guidance channels promote regeneration of the transected rat dorsal root.

Dorsal roots have a limited regeneration capacity after transection. To improve nerve regeneration, the growth-promoting effects of the neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were evaluated. The proteins were continuously released by synthetic nerve guidance channels bridging a 4-mm gap in the transected dorsal root. Four weeks after lesion, the regenerated nerve cables were analyzed for the presence of myelinated and unmyelinated axons. While BDNF showed a limited effect on axonal regeneration (863 +/- 39 axons/regenerated nerve, n = 6), NGF (1843 +/- 482) and NT-3 (1495 +/- 449) powerfully promoted regeneration of myelinated axons compared to channels releasing the control protein bovine serum albumin (293 +/- 39). In addition, NGF, but not BDNF nor NT-3, had a potent effect on the regeneration of unmyelinated axons (NGF, 55 +/- 1.4; BDNF, 4 +/- 0.3; NT-3, 4.7 +/- 0.3 axons/100 microm(2); n = 6). The present study suggests that synthetic nerve guidance channels slowly and continuously releasing the neurotrophins NGF and NT-3 can overcome the limited regeneration of transected dorsal root.

The copper chelator d-penicillamine delays onset of disease and extends survival in a transgenic mouse model of familial amyotrophic lateral sclerosis.

A subpopulation of familial cases of amyotrophic lateral sclerosis has been linked to mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). There is in vitro evidence that certain SOD1 mutants, in addition to their normal dismutation function, show increased ability of the enzyme to act as a peroxidase. This reaction is sensitive to inhibition by copper chelators. To test this hypothesis in vivo, we administered the copper chelator d-penicillamine to a transgenic mouse model of familial amyotrophic lateral sclerosis overexpressing a mutated form of human SOD1. We demonstrate that oral administration of d-penicillamine is able to delay the onset of the disease and extend the survival of these mice. Histological studies also showed a decreased loss of facial motor neurons in d-penicillamine-treated transgenic mice, corroborating the slower evolution of the disease in these animals. These results suggest that copper chelators may benefit patients with familial amyotrophic lateral sclerosis linked to mutations in the SOD1 gene.

Improved nerve regeneration through piezoelectric vinylidenefluoride-trifluoroethylene copolymer guidance channels.

Piezoelectric materials generating electrical charges in response to mechanical strain may be used to stimulate axonal regeneration following nerve injury. Tubular nerve guidance channels were extruded from a vinylidenefluoride-trifluoroethylene copolymer using a melt-extrusion process. Unlike vinylidenefluoride homopolymer, the copolymer does not need mechanical stretching to achieve a dipole-containing crystal structure, enabling the fabrication of complex piezoelectric devices. Selected tubes were rendered piezoelectric in a high voltage corona poling apparatus. Crystal structure changes induced by poling were evaluated with differential scanning calorimetry. In contrast to unpoled samples, poled ones displayed a sharp endothermic peak and a greater heat of transition at the Curie temperature, indicative of an increase in crystal order and size. The piezoelectric output of poled tubes was characterized using a laser-monitored deflection system interfaced with a charge amplifier and oscilloscope. Poled tubes generated significant voltages in response to slight mechanical deformations. The magnitude of electrical output was independent of the poling polarity. Unpoled tubes showed no electrical output. Positive, negative and unpoled vinylidenefluoride-trifluoroethylene copolymer tubes were used to repair a 10 mm gap in transected sciatic nerves of adult rats. Nerves regenerated in positively poled channels had a significantly greater number of myelinated axons than those regenerated in unpoled channels 4 wk post-implantation. Negatively poled channels contained an intermediate number of myelinated axons. We concluded that piezoelectrically active vinylidenefluoride-trifluoroethylene copolymer tubes significantly enhance nerve regeneration as compared to chemically identical, unpoled tubes and that the polarity of the corona poling procedure used to fabricate piezoelectric materials may play a role in determining biological responses.

Comparison of prehospital conventional and simultaneous compression-ventilation cardiopulmonary resuscitation.

Nine hundred ninety-four patients were enrolled in a field trial in which ambulance crews were randomly assigned to use simultaneous compression-ventilation (SC-V) CPR or conventional CPR procedures in the prehospital setting. Survival to hospital admission and to discharge was superior in the conventional CPR group vs. the experimental group (p less than .01). In a subset of adult cases whose causes of arrest were nontraumatic, survivor rates still favored the conventional CPR group: 33.5% of 337 vs. 22.5% of 365 (p less than .001). In limited cases where cardiac arrest was due to other heart disease, was vascular in origin or secondary to other natural diseases or from hypertensive cardiovascular disease, or when ECG on arrival was an agonal rhythm, survival was better (but not statistically significantly) in the experimental group. There were no statistically significant differences in the Glasgow coma scores between surviving patients in either group at 24 h post-hospital admission or discharge. It is concluded that survival in the SC-V CPR group was lower, likely reflecting a deleterious effect of the experimental technique of resuscitation. Also noted was that 14% of the control patients and 6% of the experimental patients survived with manual CPR alone.

A prospective evaluation of field categorization of trauma patients.

We prospectively evaluated the efficacy of comprehensive field triage in 8,891 trauma patients transported to trauma centers in Dade County, Florida, over a 1-year period ending in September 1986. There were 5,685 males (63.9%) and 3,206 females (36.1%) with a mean age of 32.4 +/- 18.4 years. The overall accuracy for identifying severe injury for the entire group was 30.2%. A Trauma Score less than or equal to 12 was the most accurate predictor of severe injury. Of 669 patients in this group, 617 (92.2%) sustained severe injury and 361 died (54.0%). High-speed (greater than 40 m.p.h.) motor vehicle accident was the most common reason for triage; however, of 2,277 in this group 201 patients (9.0%) had severe injury and four patients (0.2%) died. Only nine deaths (0.9%) occurred in 1,004 patients with penetrating trauma whose Trauma Scores were greater than 12. Of the 8,891 patients 4,791 (53.9%) had moderate to severe injury. The overtriage rate was therefore 46.1% using this field categorization system.

Complications of cardiac resuscitation.

In a prospective study of the complications of cardiac resuscitation, 705 cases were autopsied to identify the cause of death and the pathologic findings attributable to cardiac resuscitation. Thoracic complications were observed in 42.7 percent of the cases. A total of 31.6 percent had rib fractures, 21.1 percent had sternal fractures, and 18.3 percent were reported as having anterior mediastinal hemorrhage; 20.4 percent of the cases had an upper airway complication. Abdominal visceral complications were noted in 30.8 percent of the cases, and pulmonary complications occurred in 13 percent of the resuscitation population. Life-threatening complications, such as heart and great vessel injuries, occurred in less than .5 percent of the cases.